BACKGROUND: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative disorders with adult onset that generally progress rapidly after the onset of symptoms. The 2 conditions are independent, but they also overlap in a significant proportion of families, including 2 families in which the disorders are reported to be linked to chromosome 9p. A locus was established between the markers D9S2154 and D9S1791 by comparing haplotypes between these families. OBJECTIVE: To determine whether additional families have ALS and FTD linked to chromosome 9p. METHODS: Families were identified in Canada and France, and genotyping was performed using sequence tagged site markers around the ALS-FTD candidate interval. RESULTS: Three new families with mapping to the chromosome 9p ALS-FTD locus were identified. Analysis of the largest family shows a peak 2-point logarithm of odds (LOD) score of 2.81 and a multipoint LOD score of 3.01. The particular candidate interval delineated by this family spans 27.1 centimorgans (cM) between markers D9S157 and D9S1805. This reduces the centromeric boundary of the candidate interval compared with previously reported values, shortening the locus to 8.1 cM (8.0 megabase pairs). A maximum multipoint LOD score of 7.22 is obtained when the 3 families are combined. CONCLUSIONS: The identification of new families enables reduction of the ALS-FTD candidate region located on chromosome 9p. The clinical features observed in these families help characterize the profiles of ALS and FTD with linkage to chromosome 9p-linked families.
BACKGROUND:Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative disorders with adult onset that generally progress rapidly after the onset of symptoms. The 2 conditions are independent, but they also overlap in a significant proportion of families, including 2 families in which the disorders are reported to be linked to chromosome 9p. A locus was established between the markers D9S2154 and D9S1791 by comparing haplotypes between these families. OBJECTIVE: To determine whether additional families have ALS and FTD linked to chromosome 9p. METHODS: Families were identified in Canada and France, and genotyping was performed using sequence tagged site markers around the ALS-FTD candidate interval. RESULTS: Three new families with mapping to the chromosome 9p ALS-FTD locus were identified. Analysis of the largest family shows a peak 2-point logarithm of odds (LOD) score of 2.81 and a multipoint LOD score of 3.01. The particular candidate interval delineated by this family spans 27.1 centimorgans (cM) between markers D9S157 and D9S1805. This reduces the centromeric boundary of the candidate interval compared with previously reported values, shortening the locus to 8.1 cM (8.0 megabase pairs). A maximum multipoint LOD score of 7.22 is obtained when the 3 families are combined. CONCLUSIONS: The identification of new families enables reduction of the ALS-FTD candidate region located on chromosome 9p. The clinical features observed in these families help characterize the profiles of ALS and FTD with linkage to chromosome 9p-linked families.
Authors: Mariely DeJesus-Hernandez; Ian R Mackenzie; Bradley F Boeve; Adam L Boxer; Matt Baker; Nicola J Rutherford; Alexandra M Nicholson; NiCole A Finch; Heather Flynn; Jennifer Adamson; Naomi Kouri; Aleksandra Wojtas; Pheth Sengdy; Ging-Yuek R Hsiung; Anna Karydas; William W Seeley; Keith A Josephs; Giovanni Coppola; Daniel H Geschwind; Zbigniew K Wszolek; Howard Feldman; David S Knopman; Ronald C Petersen; Bruce L Miller; Dennis W Dickson; Kevin B Boylan; Neill R Graff-Radford; Rosa Rademakers Journal: Neuron Date: 2011-09-21 Impact factor: 17.173
Authors: Justin P Pearson; Nigel M Williams; Elisa Majounie; Adrian Waite; Jennifer Stott; Victoria Newsway; Alex Murray; Dena Hernandez; Rita Guerreiro; Andrew B Singleton; James Neal; Huw R Morris Journal: J Neurol Date: 2010-11-12 Impact factor: 4.849
Authors: Véronique V Belzil; Hussein Daoud; William Camu; Michael J Strong; Patrick A Dion; Guy A Rouleau Journal: Eur J Hum Genet Date: 2012-06-27 Impact factor: 4.246
Authors: Kyle B Womack; Ramon Diaz-Arrastia; Howard J Aizenstein; Steven E Arnold; Nancy R Barbas; Bradley F Boeve; Christopher M Clark; Charles S DeCarli; William J Jagust; James B Leverenz; Elaine R Peskind; R Scott Turner; Edward Y Zamrini; Judith L Heidebrink; James R Burke; Steven T DeKosky; Martin R Farlow; Matthew J Gabel; Roger Higdon; Claudia H Kawas; Robert A Koeppe; Anne M Lipton; Norman L Foster Journal: Arch Neurol Date: 2010-11-08
Authors: Nicola J Rutherford; Michael G Heckman; Mariely Dejesus-Hernandez; Matt C Baker; Alexandra I Soto-Ortolaza; Sruti Rayaprolu; Heather Stewart; Elizabeth Finger; Kathryn Volkening; William W Seeley; Kimmo J Hatanpaa; Catherine Lomen-Hoerth; Andrew Kertesz; Eileen H Bigio; Carol Lippa; David S Knopman; Hans A Kretzschmar; Manuela Neumann; Richard J Caselli; Charles L White; Ian R Mackenzie; Ronald C Petersen; Michael J Strong; Bruce L Miller; Bradley F Boeve; Ryan J Uitti; Kevin B Boylan; Zbigniew K Wszolek; Neill R Graff-Radford; Dennis W Dickson; Owen A Ross; Rosa Rademakers Journal: Neurobiol Aging Date: 2012-07-26 Impact factor: 4.673